Recent evoked potential studies suggested that increased motor cortex (MC) excitability provides a common mechanism for generalized motor seizures during sleep or on awakening from sleep in two feline models of epilepsy. Differences in the timing of seizures appeared to be regulated by corticopetal pathways originating in different diencephalic structures. Ventral lateral (VL) thalamic hyperexcitability seemed to trigger sleep-activated seizures in the amygdala kindling model of secondary generalized temporal lobe epilepsy. A motor-related arousal system in the posterior lateral hypothalamic area (PLH), is hypothesized to trigger seizures on awakening in the systemic pencillin model of primary generalized, myoclonic petit mal epilepsy. The proposed work will examine spontaneous and evoked extracellular unit activity in chronic, behaving cats to verify state dependent changes in excitability in VL, PLH and MC in experimental epilepsy (kindling and penicillin) and will examine effects of temporal lobe and petit mal anticonvulsants and sleep deprivation on these structures as well. Projection cells in VL, PLH and MC will be distinguished from interneurons by antidromic stimulation, and spontaneous discharge rates will be assessed throughout the sleep-wake cycle in all experiments. Neuronal excitability will assessed by quantifying orthodromic responses evoked from cortical or brain stem sites. The latency and magnitude of initial stimulus-evoked excitation, postexcitatory discharge suppression and subsequent rebound excitation will be quantified from on-line peristimulus histograms (PSTHs) constructed for each orthodromically driven cell. The results could identify separate anatomical substrates underlying sleep vs. arousal activated motor seizures in two dissimilar models of epilepsy and should further specify whether the mechanism involves a direct increase in excitability, a reduction in inhibition or both. The findings should also indicate whether the opposing effects of anticonvulsant drugs and sleep deprivation on seizure susceptibility are mediated through the same or different anatomical pathways and cell mechanisms implicated in the timing of seizures. Anticipated results will provide a neuroanatomical focus in the search for mechanisms underlying state dependent seizures and may suggest specific directions for future work at the intracellular and biochemical level.